DEVELOPMENTAL TOXICOLOGY EXPLORATORY (R21) RESEARCH GRANTS
Release Date: June 14, 2001
RFA: RFA-ES-01-006
National Institute of Environmental Health Sciences
(http://www.niehs.nih.gov)
The American Chemistry Council
(http://www.americanchemistry.com)
Letter of Intent Date: July 17, 2001
Application Receipt Date: August 17, 2001
THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS. IT INCLUDES
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.
PURPOSE
Recent advances in developmental biology, molecular biology and genomics
present unique and timely opportunities to examine the site and mechanism of
action of potential environmental developmental toxicants and to thereby set
the stage for intervention and prevention strategies. The overall objective
of this Request for Applications (RFA) is therefore to stimulate research on
the mechanism of action of developmental toxicants using the state of the art
tools of genomics, proteomics and model organisms including transgenic and
gene knock out genetic animal models. This objective will be achieved by
stimulating the interaction/collaboration of developmental toxicologists with
developmental biologists, molecular biologists and geneticists in order to
fully integrate these new research directions and to expand our knowledge on
the mode of action of developmental toxicants. The new information obtained
from these interactions will be used to accelerate research in developmental
toxicology, advance new approaches in molecular epidemiology and improve
qualitative and quantitative risk assessment processes for evaluating the
potential for exposure induced developmental defects.
This RFA is jointly supported by the National Institute of Environmental
Health Sciences (NIEHS) and the American Chemistry Council (ACC). The NIEHS
supports research into the role of environmental agents in the etiology of
disease and dysfunction. The ACC is a not-for-profit organization
established with the funding support of member companies of the U.S. chemical
industry. The ACC has affirmed its commitment to Responsible Care ® and the
American Public’s right to know by initiating a Long-Range Research
Initiative (LRI) program support by $100 million over a five-year period.
The LRI seeks to increase the knowledge of the potential risks that chemicals
have on human health and the environment. Thus, this RFA is a unique
collaboration of Government and Industry interested in improving the health
of the American people by improving the quantity and the quality of the data
on potential developmental toxicants that is available for use in the risk
assessment process.
HEALTHY PEOPLE 2010
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010," a PHS
led national activity for setting priority areas. This RFA: “Developmental
Toxicology Exploratory (R21) Research Grants," is related to several areas of
emphasis in the disease prevention objectives. Potential applicants may
obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government. Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.
SPECIAL REQUIREMENTS
Letter of Authorization
Because the domestic applications will be co-funded by the National
Institutes of Health (NIH) and the American Chemistry Council (ACC), all
applicants should submit a brief letter to the NIH indicating that the
application and the summary statements for such applications can be shared
with the ACC. Letters of authorization should be prepared by the Principal
Investigator and co-signed by the official for the applicant organization.
This letter should be submitted as a cover letter accompanying the
application.
Periodic Meetings
Upon initiation of this program, the NIH and the American Chemistry Council
plans to sponsor periodic meetings to encourage exchange of information among
investigators, to foster collaborative efforts among program grantees, and to
identify resources that would enhance the productivity of grantees. For this
purpose, applicants should request travel funds for a two-day meeting each
year, the timing and location of which will be announced. Applicants should
include in their applications a statement indicating their willingness to
participate in such meetings and, as appropriate, to cooperate with other
researchers.
MECHANISM OF SUPPORT
This RFA will use the NIH R21 Exploratory/Developmental award mechanism. The
objective of the Exploratory/Developmental Grant (R21) mechanism is to
encourage applications for one-time grants to support innovative, high-
risk/high-impact research requiring preliminary testing or development;
exploration of the use of approaches and concepts new to a particular
substantive area; research and development of new technologies, techniques or
methods; or initial research and development of data upon which significant
future research may be built. Applications will be considered as high impact
if they demonstrate the potential for ground-breaking, precedent-setting
significance, and high risk because they either lack sufficient preliminary
data to ensure their feasibility, or involve using a new model system or
technique. While this RFA is intended to encourage innovation and high impact
research, and while minimal preliminary data are expected to be described in
the application, applications should clearly indicate that the proposed
research and/or development is scientifically sound, that the qualifications
of the investigators are appropriate, and that resources available to the
investigators are adequate. As the R21 grant project cannot be renewed; if
sufficient data are generated during the term of the award, investigators
could then apply for further funding through regular research grant, e.g.,
the research project grant (R01) mechanism.
Specific application instructions have been modified to reflect the purpose
and nature of this mechanism, as well as to accommodate the "Modular Grant"
and "Just-In-Time" streamlining efforts being implemented by the NIH.
Complete and detailed instructions and information on Modular Grant
applications can be found at the website
http://grants.nih.gov/grants/funding/modular/modular.htm.
FUNDS AVAILABLE
The total estimated funds available for this RFA is approximately $2 million
that will support up to 15 awards. The annual funding plans of the NIEHS and
the ACC have included, respectively, $1.5 million and $500,000 for each of
two years to fund applications awarded in response to this RFA. This level
of support is dependent on the receipt of a sufficient number of applications
of high scientific merit. Awards will be for up to $100,000 per year (direct
costs) for up to two years. The amount and time must be justified in the
application.
BACKGROUND
This RFA is jointly supported by the National Institute of Environmental
Health Sciences (NIEHS) and the American Chemistry Council (ACC), U.S.A. The
NIEHS supports research into the role of environmental agents in the etiology
of disease and dysfunction. The support of research on reproductive and
developmental toxicology is a primary area of interest to the mission of the
NIEHS. The ACC is an independent, not-for-profit organization established
with the funding support of member companies of the U.S. chemical industry.
The ACC has affirmed its commitment to Responsible Care? and the American
Public’s right to know by initiating a Long-Range Research Initiative (LRI)
program supported by $100 million over a five-year period. The LRI seeks to
increase the knowledge of the potential risks that chemicals have on human
health and the environment. The present initiative RFA addresses the mutual
research goals of the NIEHS and the ACC to improve the quantity, quality, and
timeliness of data from investigations on the mechanisms of developmental
toxicants. Thus, this jointly sponsored RFA represents a unique collaboration
of Government and Industry to support novel, high potential research that
will contribute to the improvement of the health of the American people by
improving the quantity and quality of the data on developmental toxicants
that is available for use in the risk assessment process.
A number of developmental components and processes involved in the
organization of a metazoan body plan are shared between invertebrates and
vertebrates, as described in a recent review (Scientific Frontiers in
Developmental Toxicity and Risk Assessment: National Academy Press,
Washington, D.C., 2000). Genes are shared across phyla that control
processes such as dorsoventral dimension; organogenesis of limbs, eyes,
heart, visceral mesoderm, and gut; cytodifferentiation in neurogenesis and
myogenesis; and segmentation. There are approximately 17 cell signaling
pathways identified that operate in early, mid, and late development in
diverse species. In invertebrates such as the fruitfly (Drosophilia sp.) and
the nematode worm (C. elegans), null (functional deletion) mutations in these
morphogenetic and signaling pathways are often lethal. In mammals (mice),
the genes encoding most components of these pathways have undergone
duplication and slight diversification, leading to redundancy in the
pathways. Null mutants are not always lethal, and may result in specific
local losses that closely resemble those associated with human developmental
defects. These defects reflect those times and places in development where a
deleted component is not overlapped by a redundant component. It is
anticipated that many of the kinds of defects that occur in developmental
programs might arise from altered cell signaling pathways leading to
alterations in selective gene expression, cell secretion, cell proliferation,
and/or cell migration.
Recent technological advances in genomics, including the recent sequencing of
the genome of the human and a number of other species, have provided valuable
information on the similarities and differences in the number and
organization of genes amongst species. The new knowledge now in hand will
allow the investigation of gene expression during development using RNA
isolated from the specific organs of embryos and fetuses of the various
species amenable to laboratory modeling. The use of DNA micro-array
technologies to assess changes in gene expression is a rapidly growing
research area that will have a large impact on many fields, including
developmental toxicology. This technology will allow a global
genomic/proteomic assessment of how an organism responds to a specific
stress, drug, or toxicant. Data generated in these experiments will provide
information on cellular networks of responding genes, help define important
target molecules and pathways for toxicity investigations, as well as
providing information on future biomarkers of toxic exposure and/or effect.
Experiments using micro-array technology will help define the complex genomic
regulatory circuitry and metabolic pathways within a cell, tissue and organ
that respond to specific stressors. This technology may be able to help
define the cascade of biochemical and molecular events that define pathways
that lead to modulation and repair of a prenatal insult, thus preventing the
occurrence of developmental toxicity.
The science of proteomics promises to take over where genomics leaves off and
provide data on tissue and time specific protein expression as well as post
translational modifications altering protein activity. Indeed, it is feasible
that the integration of functional genomics and proteomics in the discipline
of metabonomics will soon provide global profiles and signatures of cellular
metabolism for advancing new approaches to metabolic toxicology, in general,
and developmental toxicology, in particular. The use of these new
technologies (genomics and proteomics) and new surrogate humanized model
systems in developmental toxicology will undoubtedly have a major impact on
toxicology research within next decade and beyond. They offer the
opportunity to markedly expand on our ability to develop a thorough
understanding of the basic mechanisms of development as well as an improved
knowledge of species differences which will undoubtedly and significantly
contribute to improved public health via protective intervention and
prevention strategies.
RESEARCH OBJECTIVES
The objectives of this RFA are to use the new technologies described in this
RFA and appropriate model organisms to develop a more complete description of
the mechanism of action of specific toxicants. This includes the toxicants’
interaction with specific molecular components of cellular or developmental
processes in the conceptus and the consequences of those interactions for the
function of the cellular or developmental process and the outcome, namely the
developmental defect, recognized as either a structural malformation or
functional deficit. It is anticipated that accomplishment of this goal will
require the interaction and collaboration of developmental biologists,
molecular biologists and developmental toxicologists. These multi-, intra-
and inter- disciplinary collaborations are strongly encouraged by this RFA.
The research objectives of the R21 mechanism used in this RFA are to support:
1) innovative, high-risk research, requiring preliminary testing or
development; 2) exploration of new approaches or concepts to a particular
substantive area; 3) research and development of new technologies, techniques
or methods; or 4) initial research and development of data upon which
significant future research may be built, i.e., the data should have a high
level of impact on the field. The project research and/or development aims
and scope can be relevant to any of the developmental toxicology science
areas relevant to the mission areas supported by the research agenda of the
NIEHS and the ACC as described below.
In general, it is expected that the new approaches proposed for this RFA will
consider the use of candidate chemicals that have been well characterized in
vivo with respect to their sites of toxicity and dose responses. This RFA,
in particular, seeks to explore a diversity of proposed modes of action and
chemical classes in order to evaluate the broadest possible range of effects
on developing embryos. The well-studied dioxin and dioxin-like substances
will not receive priority consideration in this regard. The molecular
approaches proposed should be related to survival (viability) or to a
structural or functional defect in the embryo or fetus in order to determine
exposures that lead to adaptation or repair verses those that lead to toxic
manifestations. Relatively few toxicants have been sufficiently evaluated for
effects on signaling pathway effects during development in mammals (e.g.,
cyclopamine and retinoic acid), but the potential for interference in these
key cell signaling pathways is considered to be highly feasible. Such
interference should be evaluated for impact on functional tissue or organ
physiology or morphogenesis in the fetus, neonate, adolescent or adult
individual. It is considered highly important that consideration be given to
whether or not the observed effects on genes or gene activity occur similarly
across species and are manifest as developmental defects. It is also
important that consideration be given to understanding the time course and
dose-response relationships between genetic, functional and morphogenetic
effects across species since these data are critically important to risk
assessment applications. To enhance the applicability to risk assessment,
study designs that use environmentally relevant doses of test chemicals are
encouraged, especially those that will provide sound data extending into the
low dose portion of the dose response curve, i.e., in the region beneath
traditionally observed NOAELs (No Observed Adverse Effect Levels) or LOAELs
(Lowest Observed Adverse Effect Levels). It is anticipated that proposals
using chemicals that have supportive data on developmental toxicity in rodent
models and/or humans will be of compelling interest in this regard.
Experimental models may include laboratory models studied for the
conservation of the cell signaling transduction pathways (Drosophilia, C.
elegans, zebrafish, etc.), species and strains normally used in toxicolology
studies, and genetically sensitized/transgenic models with altered signal
transduction pathways. In any event, any application that is submitted in
response to this RFA should include appropriate justification(s) for the
selection of chemical(s), dose(s) and experimental model(s).
Applications are solicited in, but not limited to, the following areas.
o Characterization of global gene expression profiles in specific
organs/tissues of model organisms associated with the normal range of
development and after a developmentally toxic exposure. The relationship
between the changes in gene expression and the developmental lesion should be
assessed.
o Use of genomic and proteomic approaches to understand the effects of
developmental toxicants on growth factor signaling and cross talk between and
among signaling pathways.
o Evaluation of specific signal transduction pathways and the associated
genetic regulatory circuits as sites of action of developmental toxicants
using model organisms and/or genomics, and the development of causal
relationships to the developmental lesion(s).
o Characterization of molecular stress and checkpoint pathways as sites of
action of developmental toxicants and the elucidation of causal relationships
between pathway alterations and dysmorphogenesis.
o Use of genomic and proteomic profiling to show species and tissue specific
toxicity of developmental toxicants that do not translate across species.
o Application of genomic and proteomic technologies to examine the role and
mechanism of oxidative damage from chemical exposure in the etiology of
dysmorphogenesis or embryo lethality.
o Use of forward and reverse mutagenesis studies in model organisms to
determine the genes altered by specific developmental toxicants and the
relationship of the altered gene activity to dysmorphogenesis.
o Use of genetically sensitized models, including transgenic and gene knock-
out animal models, to determine the potential for interactions between
chemical exposures and genetic susceptibility that increase the risk for
developmental toxicity.
o Use of microarray and proteomic analysis to examine the effects of
mixtures of toxicants with similar or different mechanisms of action and to
compare the molecular results with dysmorphogenesis caused by the mixtures
and individual components.
o Analysis of systems responsible for the metabolism and transport of
chemicals to the fetal compartment and their relationship to differences in
embryonic survival, morphogenesis, or functional defects leading to
morbidity.
o The use of genomic approaches to examine fetal programming of
modifications associated with exposure(s) to (an) environmental agent(s)
during development that may result in functional changes later in life.
It should be noted that for the purpose of this RFA research is limited to
animal models and in vitro approaches that will provide mechanistic
information on exposure to environmental agents during development and how
that leads to lethality or dysmorphogenesis. Proposals to screen chemicals
without regard to related studies on the specific mechanism of actions of the
chemical(s) studied are not responsive to this RFA and will not be accepted.
Epidemiological and clinical studies are considered non-responsive to this
specific RFA. It is anticipated that such research may be the focus of
future RFA initiatives.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups and
their sub-populations must be included in all NIH-supported biomedical and
behavioral research projects involving human subjects, unless a clear and
compelling rationale and justification are provided indicating that inclusion
is inappropriate with respect to the health of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of 1993
(Section 492B of Public Law 103-43).
All investigators proposing research involving human subjects should read the
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research," published in the NIH Guide for Grants and Contracts on
August 2, 2000
(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html);
a complete copy of the updated Guidelines is available at
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm
The revisions relate to NIH defined Phase III clinical trials and require: a)
all applications or proposals and/or protocols to provide a description of
plans to conduct analyses, as appropriate, to address differences by
sex/gender and/or racial/ethnic groups, including subgroups if applicable;
and b) all investigators to report accrual, and to conduct and report
analyses, as appropriate, by sex/gender and/or racial/ethnic group
differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age of 21)
must be included in all human subjects research conducted or supported by the
NIH unless there are scientific and ethical reasons not to include them.
This policy applies to all initial (Type 1) applications submitted for
receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should read the
"NIH Policy and Guidelines on the Inclusion of Children as Participants in
Research Involving Human Subjects" that was published in the NIH Guide for
Grants and Contracts, March 6, 1998, and is available at:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators also may obtain copies of these policies from the program staff
listed under INQUIRIES. Program staff may also provide additional relevant
information concerning the policy.
URLS IN NIH GRANT APPLICATIONS OR APPENDICES
All applications and proposals for NIH funding must be self-contained within
specified page limitations. Unless otherwise specified in an NIH
solicitation, internet addresses (URLs) should not be used to provide
information necessary to the review because reviewers are under no obligation
to view the Internet sites. Reviewers are cautioned that their anonymity may
be compromised when they directly access an Internet site.
PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT
The Office of Management and Budget (OMB) Circular A-110 has been revised to
provide public access to research data through the Freedom of Information Act
(FOIA) under some circumstances. Data that are (1) first produced in a
project that is supported in whole or in part with Federal funds and (2)
cited publicly and officially by a Federal agency in support of an action
that has the force and effect of law (i.e., a regulation) may be accessed
through FOIA. It is important for applicants to understand the basic scope of
this amendment. NIH has provided guidance at:
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm
Applicants may wish to place data collected under this RFA (PA) in a public
archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the
application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.
LETTER OF INTENT
Prospective applicants are asked to submit, by July 6, 2001, a letter of
intent that includes a descriptive title of the proposed project, the name,
address, and telephone number of the Principal Investigator, the identities
of other key personnel and participating institutions if planned
collaborations are known, and the number and title of this RFA. Although a
letter of intent is not required, is not binding, and does not enter into the
review of subsequent application, the information that it contains allows
NIEHS staff to estimate the potential review workload and plan the review.
The letter of intent is to be sent to:
Ethel B. Jackson, D.D.S.
Chief, Scientific Review Branch (EC-30)
Division of Extramural Research and Training
Office of Program Operations
National Institute of Environmental Health Sciences
P.O. Box 12233, 111 T.W. Alexander Drive
Research Triangle Park, NC 27709
Telephone: (919) 541-7846
FAX: (919) 541-2503
Email: jackson4@niehs.nih.gov
APPLICATION PROCEDURES
Applicants are strongly encouraged to contact the program contacts listed
under INQUIRIES with any questions regarding their proposed project.
The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants with the modifications noted below. Application
kits are available at most institutional offices of sponsored research and
may be obtained from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC-7910,
Bethesda, MD 20892-7910, telephone 301/435-0714, email GrantsInfo@nih.gov.
Applications are also available on the World Wide Web at:
http://grants.nih.gov/grants/forms.htm
SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS
The modular grant concept establishes specific modules in which direct costs
may be requested as well as a maximum level for requested budgets. Only
limited budgetary information is required under this approach. The just-in-
time concept allows applicants to submit certain information only when there
is a possibility for an award. It is anticipated that these changes will
reduce the administrative burden for the applicants, reviewers, and Institute
staff.
The following instructions are to be used in conjunction with the information
accompanying application form PHS 398 (rev. 4/98); they refer only to
selected items in the application form. All PHS 398 requirements should be
followed, with the exception of those items affected by the following
instructions. Applications not conforming to the requested format will be
returned to the applicant without review.
FACE PAGE
Item 2, Check the box marked “Yes” and type the RFA code number (RFA ES-01-
006) and title ( Developmental. Toxicology Exploratory Grants (R21) Program)
on this line.
Item 6: Up to a total of two years of support may be requested.
Items 7a and 7b: These items should be completed indicating Direct Costs
($100,000) and Total Costs [$100,000 plus Facilities and Administrative (F&A)
costs] for the initial budget period.
Items 8a and 8b: These items should be completed indicating the Direct
(i.e., $200,000) and Total Costs (i.e., $200,000 plus F&A) for the entire
proposed period of support.
DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD
Do not complete Form Page 4 of the PHS 398. It is not required and will not
be accepted with the application.
BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT
Do not complete the categorical budget table on Form Page 5 of the PHS 398.
It is not required and will not be accepted with the application.
NARRATIVE BUDGET JUSTIFICATION
Prepare a Modular Grant Budget Narrative page. (See
http://grants.nih.gov/grants/funding/modular/modular.htm for sample pages.)
At the top of the page, enter the total direct costs requested for each year.
This is not a Form page.
Under Personnel, list all project personnel, including their names, percent
of effort, and roles on the project. No individual salary information should
be provided. However, the applicant should use the NIH appropriation language
salary cap and the NIH policy for graduate student compensation in developing
the budget request.
For Consortium/Contractual costs, provide an estimate of total costs (direct
plus facilities and administrative) for each year, each rounded to the
nearest $1,000. List the individuals/organizations with whom consortium or
contractual arrangements have been made, the percent effort of all personnel,
and the role on the project. Indicate whether the collaborating institution
is foreign or domestic. The total cost for a consortium/contractual
arrangement is included in the overall requested modular direct cost amount.
Include the Letter of Intent to establish a consortium.
BIOGRAPHICAL SKETCH
The Biographical Sketch provides information used by reviewers in the
assessment of each individual's qualifications for a specific role in the
proposed project, as well as to evaluate the overall qualifications of the
research team. A biographical sketch is required for all key personnel,
following the instructions below. No more than three pages may be used for
each person. A sample biographical sketch may be viewed at:
http://grants.nih.gov/grants/funding/modular/modular.htm.
- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years;
- List selected peer-reviewed publications, with full citations
CHECKLIST
This page should be completed and submitted with the application. If the F&A
rate agreement has been established, indicate the type of agreement and the
date. All appropriate exclusions must be applied in the calculation of the
F&A costs for the initial budget period and all future budget years. The
applicant should provide the name and phone number of the individual to
contact concerning fiscal and administrative issues if additional information
is necessary following the initial review.
OTHER SUPPORT
Do not complete this section. It is not required and will not be accepted
with the application.
RESEARCH PLAN
Do not exceed a total of 10 pages inclusive of the following sections:
Specific Aims; Background and Significance; Preliminary Studies/Progress
Report (evidence of feasibility); and Research Design and Methods. Pertinent
subject selection and recruitment information (e.g., inclusion of women,
minorities, children), as it impacts on study design, should also be
included. Tables, figures and photographs are included in the 10 page
limitation.
Item a, SPECIFIC AIMS
The applicant should begin with a statement that justifies the designation of
the application as an Exploratory/Developmental Research Grant as defined
under the PURPOSE section of this program announcement.
The instructions for this section suggest that the applicant state “the
hypotheses to be tested.” Since some applications submitted in response to
this RFA may also be design- or problem-driven (e.g., development of novel
technologies), or need-driven (initial research to develop a body of data
upon which future research will build), hypothesis testing per se may not be
the driving force in developing such a proposal and, therefore, may not be
applicable. Thus, the application should state the hypotheses, design,
problem and/or need which will drive the proposed research. Submission of an
application under this RFA precludes concurrent submission to the NIH of
another application containing substantially the same research plan.
Item b, BACKGROUND AND SIGNIFICANCE
In this section it is important to identify clearly how the application
addresses the specific objectives of this program announcement. For example,
identify briefly how this application relates to the purpose of the R21
mechanism as stated in this RFA (i.e., highly innovative, high risk/high
impact research; exploration of the use of approaches and concepts new to a
particular substantive area; research and development of new technologies,
techniques or methods; or initial research and development of a body of data
upon which significant future research may be built).
Item c, PRELIMINARY STUDIES/PROGRESS REPORT
Minimal preliminary data are expected for an Exploratory/Developmental Grant
application.
Item d, RESEARCH DESIGN AND METHODS
Fully describe the research design and methods. In many cases, an
Exploratory/Developmental Grant mechanism will support novel research in an
area or the research and development of new technologies. Where appropriate,
specific criteria by which to judge the feasibility of novel approaches
(including milestones that will mark progress) should be explicitly described
in this section.
LITERATURE CITED
APPENDIX
Appendix materials may not be used to circumvent the page limitations.
Letters of support are not part of the appendix. However, letters of support
may be used to establish the Principal Investigator's research as separate
and distinct from those of a former mentor or to denote collaborative or
consultant relationships. Up to three publications, submitted manuscripts or
abstracts may also be included. Five copies of appendix materials should be
submitted. (Refer to PHS 398 application for additional Appendix
guidelines.)
The RFA label available in the PHS 398 (rev 4/98) application form must be
affixed to the bottom of the face page of the application. Type the RFA
number on the label. Failure to use this label could result in delayed
processing of the application such that it may not reach the review committee
in time for review. In addition, the RFA title and number must be typed on
line 2 of the face page of the application form and the YES box must be
marked.
The sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf
has been modified to allow for this change. Please note this is in pdf form.
Submit a signed, typewritten original of the application, including the
Checklist, and three signed, photocopies, in one package to:
CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
At the time of submission, please send two additional copies of the
application to:
Ethel B. Jackson, D.D.S.
Chief, Scientific Review Branch (EC-30)
Division of Extramural Research and Training
Office of Program Operations
National Institute of Environmental Health Sciences
P.O. Box 12233, 111 T.W. Alexander Drive
Research Triangle Park, NC 27709
Telephone: (919) 541-7846
FAX: (919) 541-2503
Email: jackson4@niehs.nih.gov
Applications must be received by the application receipt date listed in the
heading of this RFA. If an application is received after that date, it will
be returned to the applicant without review.
The Center for Scientific Review (CSR) will not accept any application in
response to this RFA that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application. The
CSR will not accept any application that is essentially the same as one
already reviewed. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an introduction addressing the previous critique.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the CSR and
for responsiveness to this RFA by NIEHS and ACC staff. Incomplete and/or
non-responsive applications will be returned to the applicant without further
consideration. Applications that are complete and responsive to the RFA will
be evaluated for scientific and technical merit by an appropriate peer review
group convened by the NIEHS in accordance with review criteria stated below.
As part of the initial merit review, all applications will receive a written
critique and undergo a process in which only those applications deemed to
have the highest scientific merit, generally the top-half of applications
under review, will be discussed, assigned a priority score, and receive a
second level of review by the National Advisory Environmental Health Sciences
(NAEHS) Council.
Review Criteria
The goals of NIH-supported research are to advance the understanding of
biological systems, improve the control of disease, and enhance health. In
the written comments reviewers will be asked to discuss the following aspects
of the application in order to judge the likelihood that the proposed
research will have a substantial impact on the pursuit of these goals. Each
of these criteria will be addressed and considered in the assignment of the
overall score, weighting them as appropriate for each application. Note that
the application does not need to be strong in all categories to be judged
likely to have major scientific impact and thus deserve a high priority
score. For example, an investigator may propose to carry out important work
that by its nature is not innovative but is essential to move a field
forward.
(1) Significance. Does this study address an important problem? If the aims
of the application are achieved, how will scientific knowledge be advanced?
What will be the effect of these studies on the concepts or methods that
drive this field?
(2) Approach. Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?
(3) Innovation. Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project challenge
existing paradigms or develop new methodologies or technologies?
(4) Investigator. Is the investigator appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the Principal Investigator and other researchers (if any)?
(5) Environment. Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed experiments
take advantage of unique features of the scientific environment or employ
useful collaborative arrangements? Is there evidence of institutional
support?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
- The adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals of the
research. Plans for the recruitment and retention of subjects will also
be evaluated.
- The reasonableness of the proposed budget and duration in relation to the
proposed research.
- The adequacy of the proposed protection for humans, animals or the
environment, to the extent they may be adversely affected by the project
proposed in the application.
SCHEDULE
Letter of Intent: July 17, 2001
Application Receipt: August 17, 2001
NIEHS Committee Review: October/November, 2001
Council Review: February 11-12, 2001
Earliest Funding: April 1, 2002
AWARD CRITERIA
Applications will compete with all other approved applications submitted in
response to this RFA for the available funds provided by the NIEHS and the
ACC. The following will be considered in making funding decisions: the
quality of the proposed project as determined by peer review; program
priority and balance among research areas solicited by this RFA and the
availability of funds.
In addition, the following factors will also be considered for applications
assigned to the NIEHS in response to this jointly sponsored NIEHS/ACC program
RFA:
o potential for ground-breaking, precedent setting significance of the
proposed research, with particular emphasis on novel and innovative
approaches that clearly require additional preliminary data for their value
to be established;
o potential to stimulate new research concepts or directions of high
importance to biomedical/behavioral problems, or providing a
technique/system of wide applicability to developmental toxicology research.
INQUIRIES
Potential applicants are encouraged to call the NIEHS staff members listed in
the program announcement regarding the areas of science relevant to this RFA
that the NIEHS/ACC program supports. The opportunity to clarify any issues or
questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Michael E. McClure, Ph.D. or Jerry Heindel, Ph.D.
Organs and Systems Toxicology Branch
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233, EC-23
111 T.W. Alexander Drive (for express/courier service)
Research Triangle Park, NC 27709
Telephone: (919) 541-1442 or (919) 541-0781
FAX: (919) 541-5064
Email: mm461n@nih.gov or heindelj@niehs.nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Jackie Russell
Grants Management Specialist
Grants Management Branch
Office of Program Operations
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P. O. Box 12233, EC-22
111 T.W. Alexander Drive, (for express/courier service)
Research Triangle Park, NC 27709
Telephone: (919) 541-0751
FAX: (919) 541-2860
Email: russell@niehs.nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.113 and 93.115. Awards are made under authorization of Sections 301 and
405 of the Public Health Service Act, as amended (42 USC 241 and 284) and
administered under NIH grants policies and Federal Regulations 42 CFR 52 and
45 CFR Part 74 and 92. This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.
The Public Health Service (PHS) strongly encourages all grant and contract
recipients to provide a smoke-free workplace and promote the non-use of all
tobacco products. In addition, Public Law 103-227, the Pro Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any portion
of a facility) in which regular or routine education, library, day care,
health care or early childhood development services are provided to children.
This is consistent with the PHS mission to protect and advance the physical
and mental health of the American people.